Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.
The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.
Hedman
A
A
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Angelin
B
B
Arvidsson
A
A
Dahlqvist
R
R
Nilsson
B
B
D000328:Adult; D001646:Bile / Q000378:metabolism*; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004386:Duodenum; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011802:Quinidine / Q000097:blood / Q000494:pharmacology*; D011803:Quinine / Q000097:blood / Q000494:pharmacology*; D013237:Stereoisomerism
D004077:Digoxin; D011803:Quinine; D011802:Quinidine